Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis (CITRIS-AH)

The purpose of this research study is to test the safety, tolerability, and effectiveness of Vitamin C (ascorbic acid) intravenous infusion when used to treat alcoholic hepatitis (inflammation of the liver from heavy alcohol use) and sepsis (life-threatening complication of an infection).

Study Overview

• Status: Completed
• Conditions: Sepsis; Alcoholic Hepatitis
• Intervention / Treatment: Drug: Vitamin C; Drug: Dextrose 5% in water

Detailed Description

Alcoholic hepatitis is inflammation of the liver due to alcohol consumption. It can cause one or more of the following symptoms such as jaundice (yellow discoloration of the eyes and skin), pain on the right side of the abdomen, and is accompanied by an enlarged liver. Sepsis is a life-threatening complication of an infection. As the body tries to fight an infection it sends chemicals into the bloodstream. These chemicals that are trying to fight the infection can cause inflammation. This inflammation can cause damage to many body systems and make them fail. Patients with alcoholic hepatitis and sepsis have low levels of Vitamin C in the bloodstream. Vitamin C has been shown to reduce inflammation and organ dysfunction in patients with severe infections.

The investigators do not yet know if Vitamin C will be effective in alcoholic hepatitis. Taking Vitamin C by mouth is not effective as a treatment in people with this condition so participants will receive the Vitamin C intravenously (IV). Participants will be randomly assigned to receive either Vitamin C or a placebo given through an IV every six hours for four days.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Alcoholic Hepatitis diagnosed by one of the following methods:

   1. liver biopsy
   2. clinical diagnosis based on history of alcohol use, presence of jaundice (yellowing of skin), blood tests indicating liver injury, and absence of other causes of liver injury (autoimmune disease, viral hepatitis, drug toxicity)
2. Suspected or proven infection
3. Presence of systemic inflammatory response to infection (fever, hypothermia (low temperature), tachycardia (fast heart rate), leukocytosis (high white blood cell count), leukopenia (low white blood cell count), high respiratory (breathing) rate, or need for mechanical ventilation (a machine to assist in breathing).

4. Presence of organ failure due to the body's response to infection indicated by any of the following:

   1. Hypotension (low blood pressure) or need for medications to raise blood pressure
   2. Arterial hypoxemia (low blood oxygen) or need for high flow of oxygen
   3. High lactate level (blood test indicating active response to infection)
   4. Low urine output despite administration of intravenous fluids
   5. Low platelet count (blood test)
   6. Coagulopathy (decreased blood clotting ability based on a blood test)
   7. High bilirubin (blood test)
   8. Mental status changes (confusion or delirium)
5. Absence of drugs present on urine or blood tests that indicate the possibility of liver damage or mental status changes from other causes

Exclusion Criteria:

1. Allergy to Vitamin C
2. Unable to provide consent
3. Age less than 18 years
4. No intravenous access (IV line) in a patient needing glucose (blood sugar) checks more than twice daily
5. Presence of diabetic ketoacidosis (a serious complication of diabetes)
6. Inability of patient, legally authorized representative and/or physician to commit to full medical support
7. Pregnancy or breast feeding
8. Life expectancy less than 24 hours
9. Active or history of kidney stone
10. History of chronic kidney disease
11. History of glucose-6-phosphate deficiency (a low blood protein that can cause red blood cells to break down)
12. Active cancer (except non-melanoma skin cancer)
13. Uncontrolled gastrointestinal bleeding
14. Other causes of liver injury such as viruses, autoimmune disease, drug toxicity
15. History of severe liver cirrhosis complications including variceal bleeding within the last 3 months, large ascites (fluid accumulation in the abdomen) or hepatocellular carcinoma (liver cancer)
16. History of organ transplantation
17. Initial AST or ALT (blood test indicating a liver problem)
18. Presence of acetaminophen or other drugs on urine or blood toxicology test
19. Non-English speaking
20. Prisoner or other ward of the state

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin C infusion (ascorbic acid); Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)	Drug: Vitamin C; 200mg/kg/24hours; Other Names: ascorbic acid; Ascor; AscA; Drug: Dextrose 5% in water; 50mL intravenously every 6 hours; Other Names: D5W
Placebo Comparator: Placebo; Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours	Drug: Dextrose 5% in water; 50mL intravenously every 6 hours; Other Names: D5W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Model for End Stage Liver Disease (MELD) Score	Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR).	Baseline and 96 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score	A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing)	Baseline and 96 hours
Changes to Level of Medical Care	Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline	up to 168 hours
Change in Aspartate Aminotransferase (AST) Level	Standard blood test used to determine the severity and nature of liver problems.	Baseline and 96 hours
Change in Alanine Aminotransferase (ALT) Level	Standard blood test used to determine the severity and nature of liver problems.	Baseline and 96 hours
Change in Total Bilirubin	Standard blood test used to determine the severity and nature of liver problems.	Baseline and 96 hours
Change in Alkaline Phosphatase	Standard blood test used to determine the severity and nature of liver problems.	Baseline and 96 hours
Change in Albumin	Standard blood test used to determine the severity and nature of liver problems.	Baseline and 96 hours
Changes to Corrected QT Interval (QTc)	An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.	Baseline and 96 hours
Changes to Urine Microscopy	Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.	Baseline and 96 hours
ICU-free Days	The number of days not spent in an intensive care unit (ICU)	Day 28
Number of Deaths Due to Any Cause	Any cause of death that is anticipated or unanticipated	Day 28
Number of Deaths Due to Any Cause	Any cause of death that is anticipated or unanticipated	Day 90
Hospital-free Days	The number of days spent outside of the hospital	Day 90
Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0	Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure)	up to 96 hours
Changes to Urine pH	Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale.	Baseline and 96 hours

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Arun J Sanyal, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2019
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): June 23, 2022

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Pathologic Processes; Alcohol-Related Disorders; Substance-Related Disorders; RNA Virus Infections; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Sepsis; Toxemia; Hepatitis; Hepatitis A; Hepatitis, Alcoholic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: HM20014364; U01AA026966 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No